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Altered expression of degranulation-related genes in CD8+ T cells in HTLV-1 infection.
MedLine Citation:
PMID:  23301858     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
HTLV-1 is the etiologic agent of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD8+ T cells may contribute to the protection or development of HAM/TSP. In this study we used SAGE methodology to screen for differentially expressed genes in CD8+ T cells isolated from HTLV-1 asymptomatic carriers (HAC) and from HAM/TSP patients, in order to identify genes involved in HAM/TSP development. SAGE analysis was conducted by pooling samples according to clinical status. The comparison of gene expression profiles between HAC and HAM/TSP libraries identified 285 differentially expressed tags. We focus on cytotoxicity and cytokines related genes due to their potential biological role in HTLV-1 infection. Our results showed that patients with HAM/TSP have high expression levels of degranulation related genes, namely GZMH and PRF1, and of the cytoskeletal adaptor PXN. We found that GZMB and ZAP70 were overexpressed in HTLV-infected patients compared to non-infected group. We also detected that CCL5 was higher in HAM/TSP group, as compared to HAC and to CT groups. Our findings showed that CD8+ T cells of HAM/TSP patients have an inflammatory and active profile. PXN and ZAP70 overexpression in HTLV-1 infected patients was described for the first time here and reinforce this concept. However, although active and abundant, CD8+ T cells are not able to completely eliminate infected cells and prevent the development of HAM/TSP and, moreover, these cells might contribute to the pathogenesis of the disease by migrating to CNS. These results should be further tested with biological functional assays to increase our understanding on the role of these molecules in the development of HTLV-1 related diseases.
Authors:
Tathiane Maistro Malta; Israel Tojal Silva; Daniel Guariz Pinheiro; Anemarie Ramos Dos Santos; Mariana Tomazini Pinto; Rodrigo Alexandre Panepucci; Osvaldo Massaiti Takayanagui; Yuetsu Tanaka; Dimas Tadeu Covas; Simone Kashima
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-10
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  -     ISSN:  1931-8405     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Faculty of Pharmaceutical Science of Ribeirão Preto - University of São Paulo, Ribeirão Preto, São Paulo, Brazil, , Hemotherapy Center of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil; tathimalta@hemocentro.fmrp.usp.br.
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